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Folding of thermolysin fragments
Journal article   Open access

Folding of thermolysin fragments

Claudio Vita, Angelo Fontana and Irwin M. Chaiken
European journal of biochemistry, v 151(1), pp 191-196
Aug 1985
url
https://doi.org/10.1111/j.1432-1033.1985.tb09085.xView
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

Circular dichroism (CD) and immunochemical measurements have been used to examine conformational properties of COOH‐terminal fragments 121–316, 206–316 and 225(226)–316 of thermolysin, and to compare these properties to those of native thermolysin and thermolysin S, the stable partially active two‐fragment complex composed of fragments 5–224(225) and 225(226)–316. In aqueous solution at neutral pH, all the COOH‐terminal fragments attain a native‐like conformation, as judged both by the content of secondary structure deduced from far‐ultraviolet CD spectra and by the recognition of rabbit polyclonal antibodies specific for the COOH‐terminal region in native thermolysin. The three fragments showed reversible cooperative unfolding transitions mediated by both heat and guanidine hydrochloride (Gdn · HCl). The phase transition curves were analyzed for Tm (temperature of half‐denaturation) and Gibbs free energies (ΔGD) of unfolding from native to denatured state. The observed order of thermal stability is 225(226)–316 ≤ 206–316 < 121–316 < thermolysin S < thermolysin. The ranking of ΔGD values for the three fragments correlates with the size of each fragment. Competitive binding studies by radioimmunoassay using 14C‐labeled thermolysin and affinity purified antibodies specific for native antigenic determinants in segment 206–316 of native thermolysin indicate that the COOH‐terminal fragments adopt native‐like conformations which are in equilibrium with non‐native conformations. These equilibria are shifted towards the native state as the fragment size increases from 225(226)–316, to 206–316, to 121–316. Fragment 225(226)–316, when combined with fragment 5–224(225) in the thermolysin S complex, adopts a more stable native‐like conformation and becomes much more antigenic. It has been shown that the degree of antigenicity of COOH‐terminal fragments towards thermolysin antibodies correlates directly with their conformational stability. The results of this study are discussed in relation to the recently proposed correlation between antigenicity and segmental mobility of globular proteins.

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Domestic collaboration
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Web of Science research areas
Biochemistry & Molecular Biology
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